Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery.

@article{Chung2012FragmentbasedDO,
  title={Fragment-based discovery of bromodomain inhibitors part 1: inhibitor binding modes and implications for lead discovery.},
  author={Chun-Wa Chung and Anthony W Dean and James M Woolven and Paul Bamborough},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 2},
  pages={576-86}
}
Bromodomain-containing proteins are key epigenetic regulators of gene transcription and readers of the histone code. However, the therapeutic benefits of modulating this target class are largely unexplored due to the lack of suitable chemical probes. This article describes the generation of lead molecules for the BET bromodomains through screening a fragment set chosen using structural insights and computational approaches. Analysis of 40 BRD2/fragment X-ray complexes highlights both shared and… CONTINUE READING